SARS-CoV-2 mRNA vaccine generates a CD8 T cell memory response in patients with haematological malignancies

ABSTRACT

Patients with haematological malignancies are prioritized for COVID-19 vaccine due to their high risk for SARS-CoV-2 infection related disease severity and mortality. Immune defects associated with malignancy and their treatment could influence vaccine driven immune response in these cancer patients. Thus, to understand T cell immunity, its long-term persistence, and correlation with antibody response, we evaluated the BNT162b2 SARS-CoV-2 mRNA vaccine-specific immune response in chronic lymphocytic leukaemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8+ T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 spike-protein showed vaccine-specific T cell activation and persistence of memory T cells up to 6 months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8+ T cell was observed in the patient group compared to the healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8+ T cells as well as the total number of T cell specificities. Altogether, 23 immunogenic epitopes were identified and a strong immunodominance was observed for the two of the spike-specific T cell epitopes restricted to HLA-A24 (NYNYLYRLF) and HLA-A2 (YLQPRTFLL) with a prevalence of 100% and 80% respectively. In summary, we mapped the vaccine-induced antigen-specific CD8+ T cells and showed a booster-specific activation and enrichment of memory T cells that could be crucial for long-term disease protection for this patient group.